This study has been transitioned to CTIS with ID 2023-509105-72-00 check the CTIS register for the current data. * To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in the Lyme disease season after completion of the primary…
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
Synonym
Health condition
Lyme disease caused by Borrelia species
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy:
Clinically- and laboratory-confirmed Lyme disease caused by B burgdorferi sensu
lato (as determined by the AC).
VE, defined as the relative risk reduction of the clinically- and
laboratory-confirmed Lyme disease cases in the VLA15 group compared to the
placebo group, from 28 days after receiving the booster dose through the end
of the Lyme disease season following the booster dose (end of October), and in
compliance with the key protocol criteria (evaluable efficacy population).
Primary Safety:
* Local reactions (pain at the injection site, redness, and swelling).
* Systemic events (fever, headache, fatigue, muscle pain, and joint pain).
* AEs.
* NDCMCs.
* SAEs.
Primary Immunogenicity (Lot-Consistency Subset):
Anti-OspA quantitative immunological assay titer.
In participants receiving all primary series and booster dose of 3 different
lots of vaccine in compliance with the key predefined criteria.
Secondary outcome
Secondary Efficacy:
* Clinically- and laboratory-confirmed Lyme disease caused by B burgdorferi
sensu lato (as determined by the AC).
VE, defined as the relative risk reduction of the clinically- and
laboratory-confirmed Lyme disease cases in the VLA15 group compared to the
placebo group, from 28 days after receiving the booster dose through the end of
the Lyme disease season following the booster dose (end of October), and in
compliance with the key protocol criteria among participants enrolled from NA
sites (evaluable efficacy population).
*Clinically- and laboratory-confirmed Lyme disease caused by B burgdorferi
sensu lato (as determined by the AC).
VE, defined as the relative risk reduction of the clinically- and
laboratory-confirmed Lyme disease cases in the VLA15 group compared to the
placebo group, from 28 days after completing the primary series through the end
of the Lyme disease season following the primary series (end of October), and
in compliance with the key protocol criteria (evaluable efficacy population).
Background summary
Lyme disease is the most prevalent vector-borne disease in humans across the
temperate regions of the northern hemisphere. Hundreds of thousands of people
in NA (US and Canada) and Eurasia are affected annually. Lyme disease can occur
at any age; however, incidence peaks in children 5 to 15 years of age and
adults >50 years of age.
Infections can occur throughout the year but primarily occur from the midspring
through summer months as these are the time periods when nymphal ticks seek
hosts for a blood meal and when humans are most likely to enter tick habitats.
Human proximity to tick habitats such as forested and shrub areas increases the
likelihood of infection as well as occupations such as forestry and hobbies
such as hunting and hiking in Lyme-endemic regions.
Lyme disease is caused by bacteria Borrelia burgdorferi which transmits to
humans during tick feeding when the Borrelia spirochetes migrate out of the
tick midgut and into the bite site, a process that occurs approximately 36 to
48 hours after attachment. The most common clinical manifestation of Lyme
disease is a gradually expanding erythematous skin rash known as erythema
migrans (EM). EM appears within days to weeks (average ~1 to 2 weeks) at the
location of a tick bite and is often accompanied by symptoms of fatigue, fever,
headache, mild stiffness of the neck, arthralgia, or myalgia. If untreated or
inadequately treated with antibiotics, the infection can disseminate via the
bloodstream to other parts of the body, where it can cause serious
manifestations affecting the nervous system (neuroborreliosis presenting as
facial palsy, meningitis, myelitis, or encephalitis), joints (recurrent or
persistent large joint synovitis), or heart (conduction abnormalities and
carditis).
In practice, personal preventive measures have had minimal impact on the
incidence of Lyme disease. Unfortunately, people infected with Borrelia can
become infected multiple times. As antibiotic therapy may not always be
curative, and Lyme disease is increasing in incidence and spreading
geographically, more reliable preventive measures, such as a vaccine, are
needed to further help reduce the risk of acquiring this potentially
devastating disease.
Currently, there is no licensed human Lyme disease vaccine available, and no
other human Lyme disease vaccine candidate is in active clinical development.
To address this unmet medical need and based on successful proof-of-concept
findings from prior OspA-based transmission-blocking vaccine studies, Pfizer
and Valneva SE have partnered to codevelop a vaccine called VLA15, which will
be investigated for the following indication:
Active immunization for the prevention of Lyme disease in individuals 5 years
of age and older.
Study objective
This study has been transitioned to CTIS with ID 2023-509105-72-00 check the CTIS register for the current data.
* To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in
the Lyme disease season after completion of the primary series vaccination and
booster dose.
* To describe the safety profile of VLA15 as measured by the percentage of
participants reporting local reactions, systemic events, AEs, NDCMCs, and SAEs.
* To demonstrate that the immune responses to the 6 serotypes induced by VLA15
are equivalent across 3 independent lots.
* To demonstrate that the immune responses to the 6 serotypes induced by VLA15
in children 5 through 17 years of age are noninferior to those in adults 18
through 44 years of age after the booster dose.
* To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in
the Lyme disease season after completion of the primary series vaccination and
booster dose in NA.
* To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in
the Lyme disease season after completion of the primary series vaccination.
* To describe the efficacy of VLA15 in reducing otherwise undiagnosed Lyme
disease seroconversion after each season.
* To describe the efficacy of VLA15 in preventing confirmed Lyme disease by
geographic region (NA and Europe separately).
* To describe the immunogenicity for all vaccine serotypes after completion of
the primary series vaccination and booster dose of VLA15.
* To describe the efficacy of VLA15 by serotype and risk factor.
* To describe the characteristics of participants diagnosed with PTLD that
occurred in the Lyme disease season after completion of the primary series
vaccination.
Study design
This is a Phase 3, multicenter, placebo-controlled, randomized,
observer-blinded trial to evaluate the safety, efficacy, immunogenicity, and
lot consistency of a 6-valent OspA-based Lyme disease vaccine, VLA15, in
healthy participants >=5 years of age. In the Netherlands, an application for
approval is being submitted for the recruitment of the adult population.
Randomization will occur after informed consent/assent and eligibility review
and will be stratified by geographic region. For participants enrolled from
European sites or Canadian sites, VLA15 from Lot 1 will be used and the
randomization ratio will be 1:1 (VLA15 from Lot 1: placebo); for participant
enrolled from US sites, VLA15 from 3 different lots will be used. The overall
study randomization ratio between VLA15 and placebo will be maintained as 1:1.
This study is designed to demonstrate that a 3-dose extended-schedule primary
vaccination series administered over ~5 to 9 months and a booster dose given
prior to the start of the second season will protect against Lyme disease
during the Lyme disease season following
the booster dose. The primary series will be completed from approximately April
to as late as August 2023 for individuals enrolled between August 2022 and
March 2023, and these participants will contribute to post-primary series case
detection during the 2023 Lyme disease season and the postbooster case
detection during the Lyme disease season in 2024.
For participants enrolled after March 2023, whose vaccinations will commence in
July 2023, the primary series will be completed from early April to early May
2024, and these participants will contribute to post-primary series case
detection during the 2024 Lyme disease season and postbooster case detection
during the Lyme disease season in 2025. The primary series will be followed by
a booster dose 1 year later, from approximately March to early May just prior
to the beginning of the second Lyme disease season.
It is expected that each participant will participate in the study for up to 30
months.
All participants will be asked at Visit 1 and periodically reminded to present
to their clinical sites for an unscheduled visit whenever experiencing
symptoms associated with Lyme disease. If the investigator has a reasonable
clinical suspicion of Lyme disease the unscheduled visit should be converted to
a suspected-Lyme disease acute visit. Targeted PE will be performed and blood
samples will be taken and tested for for the presence of borrelial infection.
If appropriate, a photograph(s) of pertinent Lyme disease-related findings will
be taken. For participants presenting with skin manifestations suspicious for
Lyme disease, a maximum of two 2-mm skin punch biopsy samples will be obtained
for further laboratory testing following provision of supplemental consent. If
other biological samples (ie, CSF/paired serum, synovial fluid) are obtained
from a participant as a part of clinical care, sites will be asked to provide
residual sample material to the sponsor. Treatment will be given on the basis
of standard of care.
A suspected Lyme disease convalescent visit will occur approximately 1 month
after the suspected-Lyme disease acute visit. At this visit, participants will
be assessed for resolution of their signs/symptoms, and an additional blood
sample will be obtained.
A confirmed Lyme disease PTLD-assessment visit will occur approximately 9 to 12
months after completion of treatment for all EAC-confirmed Lyme disease cases
identified in the Lyme disease season following the primary series only.
Intervention
Intervention Name: PF-07307405 (VLA15) (Vaccine) // Normal Saline (Placebo)
Unit dose strength: 0,5mL
Route of Administration: Intramuscular injection
IMP
Sourcing: Provided centrally by the sponsor
Packaging and labeling: Study intervention will be provided in pre-filled
syringes (PFSs). Each PFS will be labeled as required per country requirement
Dosing:
Dose 1 (Start of Primary Series: Day 1)
Dose 2 (50-70 Days After Visit 1)
Dose 3 (End of Primary Series: 1-Month Period Prior to First Lyme Disease
Season)
Booster Dose (2-Month Period Prior to Second Lyme Disease Season)
Study burden and risks
Common AEs noted after vaccination with the study intervention VLA15 are
primarily related to reactogenicity, including local reactions (pain,
tenderness, swelling, induration/hardening, itching, and erythema/redness
around the injection site) and systemic events (headache, fatigue, myalgias,
arthralgias, chills, fever, rash, and flu-like symptoms).
The safety profile is largely derived from Phase 2 studies.
As with any vaccine, an allergic reaction may occur. Symptoms of an allergic
reaction can include swelling of the lips, mouth, and throat, which may cause
difficulty in swallowing or breathing; skin rash; swelling of the hands, feet,
and ankles; dizziness; and fainting. A severe allergic shock (anaphylactic
shock) may occur.
Risks that may be associated with study procedures include risk from
venipuncture blood sampling, such as feeling faint, dizziness, fainting, pain,
swelling, bruising, and infection in the vicinity of the vein from where blood
is taken. Risks associated with skin punch biopsies are the same as those for
venipuncture in addition to scarring at the biopsy site, the possibility of
requiring a suture, and allergic reaction (including anaphylaxis and death) to
local anesthesia. There may also be additional risks associated with the
vaccines administered during the study, which are unknown at this time.
Safety assessments described in this protocol and ongoing safety data reviews
by the investigator, the sponsor*s global medical monitor, the internal risk
management committee, and the external DMC will serve to monitor and mitigate
these risks.
OspA ST1-based vaccines have been shown to be protective against Lyme disease
in humans previously in 2 independent efficacy studies, thus validating the
mechanism and OspA target. VLA15 was effective in animal models and induced
immune responses in the majority of study participants in Phase 1 and 2
studies. However, as VLA15 is a new multivalent construct that has not yet been
tested for clinical efficacy, the participants might not directly benefit from
vaccination with VLA15.
Benefits to individual participants include:
* Active surveillance for and access to evaluation and treatment of Lyme
disease.
* Clinical assessment by a medical provider at the start of the study and at
additional time points (disease visits) throughout the study.
* Evaluations and management of some illnesses (AEs) that occur during
participation in the study
* Receipt of a vaccine that may potentially prevent Lyme disease.
Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the
potential risks identified in association with VLA15 primarily include
well-established local reactions and systemic events common to many vaccines
and that are mostly mild to moderate in severity and transient in nature, or
minor complications expected from procedures (vaccination, venipuncture, skin
punch biopsy), and are justified by the anticipated benefits that may be
afforded to healthy adult and pediatric participants.
Rivium Westlaan 142
Capelle a/d IJssel 2909LD
NL
Rivium Westlaan 142
Capelle a/d IJssel 2909LD
NL
Listed location countries
Age
Inclusion criteria
1.Male or female participants >= 5 years of age at enrolment (younger population
only recruited in countries that have received full regulatory approval).
Type of Participant and Disease Characteristics:
2.Participants who reside in areas with endemic Lyme disease and who lead
lifestyles that put them at increased risk for Lyme disease.
3.Participants or participants' parent(s)/legal guardian(s), who are willing
and able to comply with all scheduled visits, investigational plan, laboratory
tests, lifestyle considerations, and other study procedures (younger population
only recruited in countries that have received full regulatory approval).
4.Healthy male and female participants at enrollment
5.Capable of giving signed informed consent, and assent (as appropriate).
Exclusion criteria
1. Pregnant female participants. Participants unwilling or unable to use
effective methods of contraception as outlined in this protocol from the
signing of the informed consent through 28 days after completion of the primary
vaccination series and from the booster dose through 28 days after the booster
vaccination.
Medical Conditions:
2. Any contraindication to vaccination or vaccine components, including
previous anaphylactic reaction to any vaccine or vaccine-related components.
3. Any diagnosis of Lyme disease within the past 3 months.
4. Any history of Lyme carditis, neuroborreliosis, arthritis, or other
disseminated Lyme disease regardless of when diagnosed.
5. Known tick bite within the past 4 weeks.
6. Newly developed or unstable underlying conditions that may interfere with
the assessment of Lyme disease, including but not limited to chronic
arthralgia/arthritis, second/third-degree AV heart block, chronic pain
syndromes, and chronic skin conditions that reduce the ability to
detect cutaneous manifestations of Lyme disease.
7. Underlying clotting deficiency (eg, bleeding disorder, thrombocytopenia)
that may increase the risk of excessive bleeding following required study
procedures.
8. Congenital or acquired immunodeficiency or treatments that would inhibit the
ability to mount an immune response to a vaccine.
9. Any unstable autoimmune condition with a manifestation (eg, arthritic and
neurologic) that may interfere with the assessment of Lyme disease (Potential
participants with well-controlled, stable autoimmune conditions under the care
of a rheumatologist are eligible).
10. Underlying bone marrow disorder such as myelodysplasia, myeloma, or
myeloproliferative disorder, treated within the past year, or any history of
bone marrow transplant.
11. Malignancy that required treatment with chemotherapy (including the use of
adjunctive and hormonal therapy), immunotherapy, radiation therapy, or
antineoplastic target therapies within the past 24 months.
12. Other medical or psychiatric condition including recent (within the past
year) or active suicidal ideation/behavior or laboratory abnormality that may
increase the risk of study participation or, in the investigator's judgment,
make the participant inappropriate for the study.
Prior/Concomitant Therapy:
13. Receipt of a previous vaccination for Lyme disease.
14. Treatment for Lyme disease in the 3 months prior to study intervention
administration.
15. Chronic systemic doxycycline or minocycline or other tetracycline class
drug use for acne or any other chronic suppressive antibiotics used to treat
other conditions.
16. Receipt of blood/plasma products or immunoglobulins within 6 months before
study intervention administration through conclusion of the study.
17. Receipt of systemic corticosteroids (>=20 mg/day of prednisone or
equivalent) for >=14 days within 28 days before study intervention
administration. Inhaled/nebulized, intra-articular, intrabursal, or topical
(skin or eyes) corticosteroids are permitted.
18. Receipt of chronic systemic treatment with other known immunosuppressant
medications, or radiotherapy, within 6 months before study intervention
administration.
19. Receipt of anticoagulant therapy within 1 month before study intervention
administration.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-509105-72-00 |
| EudraCT | EUCTR2021-005427-20-NL |
| ClinicalTrials.gov | NCT05477524 |
| CCMO | NL80806.000.22 |